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[摘要]
目的研究苦参碱对高胆固醇血症大鼠心肌缺血性损伤的保护作用,并探讨其作用机制。方法SD大鼠给予高胆固醇饮食4周后,sc异丙肾上腺素(ISO,85mg/kg,每日1次,连续2d)建立高胆固醇血症心肌缺血性损伤模型,观察苦参碱对模型大鼠血脂、心功能、心肌损伤标志酶及抗氧化酶等的影响。结果苦参碱(50、100和200mg/kg)可降低模型大鼠血清胆固醇(TC)和甘油三酯(TG)水平;改善大鼠左心室收缩(升高LVSP和+dp/dtmax)和舒张功能(降低LVEDP和升高-dp/dtmax);减少血清心肌损伤标志酶:乳酸脱氢酶(LDH)和肌酸激酶(CK)的量;提高血清及心肌组织中抗氧化酶:超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-PX)的活力,并相应降低脂质过氧化物丙二醛(MDA)量。组织病理学结果显示,苦参碱可减轻高胆固醇血症大鼠缺血性心肌组织形态学结构的异常改变。结论苦参碱对高胆固醇血症大鼠缺血性心肌结构与功能具有保护作用,其作用机制与降低血清TC和/或TG,提高机体抗氧化酶活性并维持心肌细胞膜稳定性有关。
[Key word]
[Abstract]
Objective To explore cardioprotective effect of matrine on myocardial ischemia in hypercholesterolemiarats Methods Myocardia nfarction was nduced by subcutaneous njection of isopreterenol(ISO,85 mg/kg)once daily for two consecutive days in rats feeding cholesterol-rich diet for 4 weeks.Content of serum lipid,myocardial injury marker enzymes,lipid peroxidatase and activities of antioxidative enzymes in serum and/or heart tissues were measured,and cardiac function was evaluated.Results Administration of matrine(50,100,and 200 mg/kg,respectively)decreased serum level of TCand TG,improved left ventricle(LV)contractile function(increased LVSP and+dp/dtmax)and LVdiastolic function(decreased LVEDP and increased--dp/dtmax),depressed the levels of myocardial injurymarker enzymes of lactic dehydrogenase(LDH)and creatine kinase(CK),promoted the activities ofantioxidative enzymes of superoxide dismutase(SOD),catalyst(CAT),and glutathione peroxidase(GHS-PX),as well as decreased the content of lipid peroxidation product of malondialdehyde(MDA)inplasma and/or myocardial tissues in hypercholesterolemia rats with myocardial infarction.Histopathologyexamination demonstrated that matrine could attenuate IS0一induced myocardial infarction morphologically in hypercholesterolemia rats. Conclusion Our results suggest that cardioprotective effect of matrine onmyocardial infarction in hypercholesterolemia rats iS attributed to its ability to decrease the TC and TGcontent of serum,enhance the activities of antioxidative enzymes,and maintain the stability of myocardialcellular membranes.
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[基金项目]
教育部新世纪优秀人才支持计划项目(NECT-06-0916);宁夏教育厅高等院校科研项目(2005-2007);宁夏自然科学基金资助项目(NZ0782)